Current cancer therapeutics often disrupt tumor growth by inhibiting rapidly proliferating cells, doing so via a variety of cytotoxic mechanisms. In fact, cells within many types of solid tumors often exhibit considerable phenotypic heterogeneity, and in some cases a certain subpopulation of cells appear to be responsible for driving tumor growth, recurrence and metastasis. The epithelial-mesenchymal transition (EMT) represents a cell-biological program that becomes activated during malignant progression and is associated with generation of invasive and cancer stem-like cells arising in epithelial tumors.
Cancer stem cells (CSCs), which possess tumor-initiating properties, have been identified within certain breast, colon, head and neck, lung and prostate carcinomas. In experimental models of cancer development, treatment of bulk cancer cells within tumors or cancer cells lines with chemo- or radiotherapy has been shown to select for the outgrowth of therapy-resistant subpopulations of cancer cells that are more tumorigenic, invasive and stem-like. Conventional cancer therapeutics tend to preferentially eliminate the non-CSCs in a tumor, leaving behind residues of CSCs that can subsequently generate clinical relapses.